Author/Authors :
Velayati، Ali Akbar نويسنده Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran Velayati, Ali Akbar , Farnia، Parissa نويسنده , , Farahbod، Amir Masoud نويسنده Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran Farahbod, Amir Masoud , Afraei Karahrudi، Mona نويسنده Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran Afraei Karahrudi, Mona , Derakhshaninezhad، Zahra نويسنده Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran Derakhshaninezhad, Zahra , Kazampour Dizaji، Mehdi نويسنده , , Sheikhghomi، Samira نويسنده Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran Sheikhghomi, Samira , Saeif، Shima نويسنده Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran Saeif, Shima
Abstract :
Introduction: The purinergic P2X7-receptors and tumor necrosis factor-alpha (TNF-?) may play important roles in the development of
pulmonary tuberculosis (PTB). Genetic contribution of the host is among the most important factors that plays a significant role in the
susceptibility of the disease. In this regard, both genes for P2X7 receptor and TNF-? have been identified as essential components of the
host immune response in the containment of TB. However, the relationship between P2X7 and TNF-? polymorphism and TB susceptibility
remains inconclusive. Objectives: This study was designed to investigate the association of P2X7 and TNF- ? gene polymorphisms among Iranian PTB patients. Materials and Methods: In a case-control study, single nucleotide polymorphisms (SNPs) in P2X7 (+1513, -762) and TNF-? (at -238, -308, -244,
-857 and -863) genes were assessed using PCR-RFLP and allele-specific PCR. Thereafter, haplotype and diplotype variability were compared
and analyzed. Results: For the 1513 loci, the heterozygosity was higher in patients (35; 44.3%) than control subjects (12; 24%) [(P = 0.026) ORS; 2.45 CI95 %
(1.13 - 5.33)]. For the -762 loci, the frequency of mutant alleles between patients and controls were not statistically significant. No statistical
difference was observed in allele frequencies of TNF -308 and -857. However, the frequency of -238 A allele was more in tuberculosis (TB) cases
(72.1%) (P = 0.000) [ORs: 5.85 (2.70 - 12.64)]. Data analysis showed greater frequency of haplotypes, i.e. TGGA-CA and CGGA-TA in the patient
(21.5%; 14.6%) than control group (2.0%; 6.0%), respectively. Additionally, the diplotype "CCGGGGGGCCAA" was significantly associated with
susceptibility to PTB [1.9 (0.08 - 48.3)]. Conclusions: In the studied population, polymorphisms in P2X7 (1513) and TNF-? (S-238) gene were associated with risk of developing PTB.
Additionally, distribution of haplotype and diplotype variables did appear to be more specific than SNPs.
